CircNDUFB2 Inhibits Non-small Cell Lung Cancer Progression Via Destabilizing IGF2BPs and Activating Anti-tumor Immunity

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Jan 13

PMID 33436560

Citations 278

Authors

Botai Li

Lili Zhu

Chunlai Lu

Cun Wang

Hui Wang

Haojie Jin

Xuhui Ma

Zhuoan Cheng

Chengtao Yu

Siying Wang

Qiaozhu Zuo

Yangyang Zhou

Jun Wang

Chen Yang

Yuanyuan Lv

Liyan Jiang

Wenxin Qin

Affiliations

Soon will be listed here.

Abstract

Circular RNAs (circRNA) are a class of covalently closed single-stranded RNAs that have been implicated in cancer progression. Here we identify circNDUFB2 to be downregulated in non-small cell lung cancer (NSCLC) tissues, and to negatively correlate with NSCLC malignant features. Elevated circNDUFB2 inhibits growth and metastasis of NSCLC cells. Mechanistically, circNDUFB2 functions as a scaffold to enhance the interaction between TRIM25 and IGF2BPs, a positive regulator of tumor progression and metastasis. This TRIM25/circNDUFB2/IGF2BPs ternary complex facilitates ubiquitination and degradation of IGF2BPs, with this effect enhanced by N-methyladenosine (mA) modification of circNDUFB2. Moreover, circNDUFB2 is also recognized by RIG-I to activate RIG-I-MAVS signaling cascades and recruit immune cells into the tumor microenvironment (TME). Our data thus provide evidences that circNDUFB2 participates in the degradation of IGF2BPs and activation of anti-tumor immunity during NSCLC progression via the modulation of both protein ubiquitination and degradation, as well as cellular immune responses.

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